Interactions Discovery Core Abstract The Interactions Discovery Core (IDC) will continue to support interactive projects focusing on cellular protein complexes mediating early events in HIV-1 infection. The projects carried out by the IDC will involve multiple components of the Center as well as outside investigators. Aim 1 proposes to identify cellular proteins binding specifically to HIV-1 capsid sites under positive selection. These highly collaborative experiments will be supported by the Protein Core and Project 3, which will provide recombinant CA and/or soluble oligomeric CA assemblies, and performed in collaboration with the HIV Virology Core, which will validate virologically high priority hits. The virologically relevant targets will subsequently enter the PCHPI structure determination pipeline. Aim 2 proposes to identify CPSF6 interacting proteins that mediate HIV-1 integration into genes; the candidate functional CPSF6 partners will be investigated further in A. Engelman's lab. Aim 3 proposes to identify novel HIV Vpr targets in DNA repair and replication pathways, and in particular those responsible for the induction of DNA damage checkpoint by Vpr. The latter experiments will be performed in collaboration with Project 6, which will validate the hits, and thereby will continue to provide the identity of new Vpr complexes with cellular proteins for mechanistic and structural studies in the PCHPI. Thus, overall, the IDC is completely integrated and central to many aspect of science being pursued at PCHPI.